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Dose response of tramadol and its combination with paracetamol in UVB induced hyperalgesia
Author(s) -
Ortner C.M.,
Steiner I.,
Margeta K.,
Schulz M.,
Gustorff B.
Publication year - 2012
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1016/j.ejpain.2011.08.007
Subject(s) - tramadol , hyperalgesia , placebo , sunburn , anesthesia , medicine , analgesic , pharmacology , nociception , dermatology , receptor , alternative medicine , pathology
Combining tramadol with paracetamol is an established analgesic treatment strategy. However, dosing and differential effects on peripheral and central hyperalgesia are still to be determined. After E thics C ommittee approval, 32 volunteers have been included in this 2 phased, double blinded, placebo controlled, cross‐over study. A defined small skin area was irradiated with a UVB source inducing hyperalgesia. Twenty‐four hours after irradiation, heat pain‐, cold pain threshold ( HPPT , CPPT ), mechanical pain sensitivity to pin prick ( MPS ) in the area of pin prick hyperalgesia ( AsH ) and MPS in the sunburn were determined. In phase I , measurements have been repeated 30 min after receiving cumulative 0.3, 0.6 and 1 mg/kg of intravenous ( i.v. ) tramadol or active placebo. Only at 1 mg/kg tramadol and solely for MPS in the sunburn a reduction to placebo could be demonstrated ( p = 0.024). Accordingly in phase II , the trial has been repeated using 1 mg/kg tramadol and paracetamol or placebo in a cumulative i.v. dose of 330, 660 and 990 mg. Now the addition of 330 mg paracetamol to tramadol reduced thermal hyperalgesia by 1.15 °C ( CI 0.55; 1.76). This effect, however, did not increase with higher doses. Tramadol showed week anti‐hyperalgesia reducing CPPT , MPS and AsH compared to baseline measurements ( p < 0.05). Paracetamol also reduced secondary hyperalgesia, but no combination effect with tramadol could be shown. We conclude, in inflammatory hyperalgesia tramadol alone exerts only weak anti‐hyperalgesia. Even adding a small dose paracetamol enhances thermal anti‐hyperalgesia.